Poly(amino acid) derivatives and cell penetrating peptide mediated synthesis of nanoparticles and their application to hearing loss therapy = 폴리아미노산 유도체와 세포투과성 펩타이드를 이용한 나노입자의 합성 및 난청 치료로의 응용

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Hearing loss was occurred due to the damage of hair cell and spiral ganglion neuron in inner ear. If hair cells were damaged, it couldn’t be regenerated. Therefore, many attempts have been tried to deliver steroids such as dexamethasone or gene for inner ear fundamental therapy. Intratympanic route has attracted a great deal of interest for local drug delivery, performed via the injection or perfusion of drugs into the middle ear and drug diffusion into the inner ear through the round window membrane (RWM). Especially, this local delivery using nanoparticle has several advantages, including high drug concentrations in inner ear fluids and the avoidance of undesirable systemic exposure. In chapter 2, three kinds of cell penetrating peptides (Penetratin, Tat, and Arg8) were examined as RWM penetration enhancers. From the their cellular uptake study in HEI-OC1 cells, Arg8 was selected as optimal CPP in inner ear cells. In chapter 3, Three types of carrier materials, PHEA-g-C18, PHEA-g-Arg8, and PHEA-g-C18-Arg8, were synthesized to examine the effects of oligoarginine and morphology of the synthesized carriers. Nile red (NR) was used as a fluorescent indicator as well as to model a hydrophobic drug. And the nanoparticles were investigated to determine whether the limitations of low drug transport levels across the round window membrane (RWM) and poor transport into inner ear target cells could be overcome. In chapter 4, the dexamethasone (Dex) loaded PHEA-g-C18-Arg8 nanoparticles were developed for the delivery of genes to draw the synergistic effect of dexamethasone and gene. The cationic PHEA-g-C18-Arg8 nanoparticles were self-assembled to create cationic micelles having a octadecylamine (C18) core cooperated with loaded Dex, and a Arg8 peptide shell for electrostatic complexation with genes (Cx 26 siRNA, GFP DNA, BDNF pDNA). Dex in PHEA-g-C18-Arg8/Dex nanoparticles would achieve the anti-inflammation effect, and enhance the gene expression as a carrier.
Kim, Jong-Dukresearcher김종득researcher
한국과학기술원 :생명화학공학과,
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학위논문(박사) - 한국과학기술원 : 생명화학공학과, 2016.8 ,[x, 109 p. :]


cell penetrating peptide; hearing loss; poly(2-hydroxyethyl L-aspartamide); drug delivery system; gene delivery system; 세포 투과성 펩타이드; 난청; 폴리하이드록실 아스팔트아미드; 약물전달시스템; 유전자전달시스템

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